title: High efficiency of ROS production by glycerophosphate dehydrogenase in mammalian mitochondria.
abstract: We investigated hydrogen peroxide production in mitochondria with low (liver, heart, brain) and high (brown adipose tissue, BAT) content of glycerophosphate dehydrogenase (mGPDH). ROS production at state 4 due to electron backflow from mGPDH was low, but after inhibition of electron transport with antimycin A high rates of mGPDH-dependent ROS production were observed in liver, heart and brain mitochondria. When this ROS production was related to activity of mGPDH, many-fold higher ROS production was found in contrast to succinate- (39-, 28-, 3-fold) or pyruvate plus malate-dependent ROS production (32-, 96-, 5-fold). This specific rate of mGPDH-dependent ROS production was also exceedingly higher (28-, 66-, 22-fold) compared to that in BAT. mGPDH-dependent ROS production was localized to the dehydrogenase+CoQ and complex III, the latter being the highest in all mitochondria but BAT. Our results demonstrate high efficiency of mGPDH-dependent ROS production in mammalian mitochondria with a low content of mGPDH and suggest its endogenous inhibition in BAT.
authors.affiliation: Department of Bioenergetics, Institute of Physiology and Center for Applied Genomics, Academy of Sciences of the Czech Republic, Vídenská 1083, Prague 4, Czech Republic.
authors.forename: Tomás
authors.initials: T
authors.lastname: Mrácek
authors.forename: Alena
authors.initials: A
authors.lastname: Pecinová
authors.forename: Marek
authors.initials: M
authors.lastname: Vrbacký
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Drahota
authors.forename: Josef
authors.initials: J
authors.lastname: Houstek
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D006224:Cricetinae; D004579:Electron Transport; D014450:Electron Transport Complex III / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019802:Succinic Acid / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D000968:Antimycin A; D019289:Pyruvic Acid; D019802:Succinic Acid; D006861:Hydrogen Peroxide; D005993:Glycerolphosphate Dehydrogenase; D014450:Electron Transport Complex III